The bioactive effect of Nitric oxide (Chemical formula NO) was found in 1992. Soon after, its effect on the human body has been extensively investigated. The most studied actions of NO are in the cardiovascular system, where it is produced by vascular endothelial and plays a crucial role in vascular tone and structure regulation. This vasodilator tone plays an important role in regulation of blood flow in healthy humans. Except its vascular dilation effect, NO has exerts an anti-atherogenic effects due to its anti-inflammatory influence, limiting the development of the complex plaque, inhibiting platelets adhesion and aggregation, preventing smooth muscle cells proliferation and migration. Given the multiple actions of NO on cardiovascular medicine, delivery of exogenous NO is an attractive therapeutic option for the treatment of atherosclerosis. NO molecule is a free radical, which has high reactivity with the oxygen in air to form nitrogen dioxide. Such chemical character of NO has led to the synthesis of a variety of NO donors. NO donors are molecular carriers of NO to stabilize the radical until its release in circulation. Each NO donor has different rates of NO release and is tailored to different drugs to suit the disease target. However, the long-term use of current NO donor is limited by development of tolerance and toxicity issues. This gives rise to a clinical need for novel alternative delivery methods (see, Miller and Megson, Recent developments in nitric oxide donor drugs. British J. Pharm. 2007; 151: 305-321, herein incorporated by reference).
NO gas itself has been directly used in pulmonary hypertension. In such specific cases, the NO is delivered by inhalation. Recently, such delivery method has been used in the treatment of restenosis. However, the systemic NO delivery might be limited by unwanted side effects outside the target tissue due to its enormous variety of effects of NO in different tissues. As such, what is needed are methods, compositions, and systems for delivery of NO to treat diseases, such as atheroclothesis, as well as methods for in vivo imaging and triggering methods such that NO can be delivered at the desired site.